Liu Jun, Gu Liming, Li Wenli
Reproductive Medicine Center, Yue Bei People's Hospital, Shantou University Medical College, Shaoguan, China.
Medical Research Center, Yue Bei People's Hospital, Shantou University Medical College, Shaoguan, China.
Front Immunol. 2022 Mar 3;13:730186. doi: 10.3389/fimmu.2022.730186. eCollection 2022.
Currently, the aetiology and pathogenesis of idiopathic pulmonary fibrosis (IPF) are still largely unclear. Moreover, patients with IPF exhibit a considerable difference in clinical presentation, treatment, and prognosis. Optimal biomarkers or models for IPF prognosis are lacking. Therefore, this study quantified the levels of various hallmarks using a single-sample gene set enrichment analysis algorithm. The hazard ration was calculated using Univariate Cox regression analysis based on the transcriptomic profile of bronchoalveolar lavage cells and clinical survival information. Afterwards, weighted Gene Co-expression Network Analysis was performed to construct a network between gene expression, inflammation response, and hypoxia. Subsequently, univariate Cox, random forest, and multivariate Cox regressions were applied to develop a robust inflammation and hypoxia-related gene signature for predicting clinical outcomes in patients with IPF. Furthermore, a nomogram was constructed to calculate risk assessment. The inflammation response and hypoxia were identified as latent risk factors for patients with IPF. Five genes, including HS3ST1, WFDC2, SPP1, TFPI, and CDC42EP2, were identified that formed the inflammation-hypoxia-related gene signature. Kaplan-Meier plotter showed that the patients with high-risk scores had a worse prognosis than those with low-risk scores in training and validation cohorts. The time-dependent concordance index and the receiver operating characteristic analysis revealed that the risk model could accurately predict the clinical outcome of patients with IPF. Therefore, this study contributes to elucidating the role of inflammation and hypoxia in IPF, which can aid in assessing individual prognosis and personalised treatment decisions.
目前,特发性肺纤维化(IPF)的病因和发病机制仍不清楚。此外,IPF患者在临床表现、治疗和预后方面存在显著差异。缺乏用于IPF预后的最佳生物标志物或模型。因此,本研究使用单样本基因集富集分析算法对各种特征的水平进行了量化。基于支气管肺泡灌洗细胞的转录组谱和临床生存信息,采用单变量Cox回归分析计算风险比。随后,进行加权基因共表达网络分析,以构建基因表达、炎症反应和缺氧之间的网络。随后,应用单变量Cox、随机森林和多变量Cox回归来开发一个强大的炎症和缺氧相关基因特征,用于预测IPF患者的临床结局。此外,构建了一个列线图来计算风险评估。炎症反应和缺氧被确定为IPF患者的潜在危险因素。鉴定出包括HS3ST1、WFDC2、SPP1、TFPI和CDC42EP2在内的五个基因,它们构成了炎症-缺氧相关基因特征。Kaplan-Meier绘图显示,在训练和验证队列中,高风险评分患者的预后比低风险评分患者更差。时间依赖性一致性指数和受试者工作特征分析表明,该风险模型可以准确预测IPF患者的临床结局。因此,本研究有助于阐明炎症和缺氧在IPF中的作用,这有助于评估个体预后和个性化治疗决策。